Odutayo Ayodele, Cherney David, Miller Judith, Ahmed Sofia B, Lai Vesta, Dunn Sheila, Pun Nicole, Moineddin Rahim, Hladunewich Michelle A
Division of Nephrology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada;
University Health Network, University of Toronto, Toronto, Ontario, Canada;
Am J Physiol Renal Physiol. 2015 Mar 15;308(6):F535-40. doi: 10.1152/ajprenal.00602.2014. Epub 2015 Jan 13.
The oral contraceptive pill (OCP) activates the renin-angiotensin-aldosterone system (RAAS) through first-pass hepatic metabolism. Although usually benign, RAAS activation may have detrimental effects on renal and hemodynamic function in some women. Since combined hormonal contraception with the transdermal patch (EVRA) does not undergo first-pass hepatic metabolism, we hypothesized that the RAAS response would be different from that of OCP subjects. Thirty-five nonsmoking, premenopausal women (15 control subjects, 10 OCP subjects, and 10 contraceptive patch subjects) without evidence of cardiovascular disease, renal disease, or diabetes were studied. Baseline angiotensinogen, renin, angiotensin II, aldosterone, and plasma renin activity were assessed along with hormonal and hemodynamic responses to simulated orthostatic stress using incremental lower body negative pressure (LBNP; -15, -25, and -40 mmHg). Baseline levels of angiotensinogen, angiotensin II, and plasma renin activity were significantly higher in OCP subjects compared with normotensive control and contraceptive patch subjects (P < 0.05), whereas aldosterone was significantly higher in OCP versus control subjects only (P < 0.05). Plasma renin levels were significantly lower at baseline in contraceptive patch subjects compared with normotensive control and OCP subjects (P < 0.05). In response to LBNP, increases in renin, angiotensin II, and aldosterone were attenuated in contraceptive patch subjects in conjunction with an exaggerated decline in mean arterial pressure (P < 0.05 vs. control and OCP subjects). The contraceptive patch in healthy premenopausal women is associated with an impaired ability to maintain blood pressure in response to LBNP, possibly due to insensitivity of the endogenous RAAS. Further evaluation may be beneficial in women with kidney disease.
口服避孕药（OCP）通过首过肝代谢激活肾素-血管紧张素-醛固酮系统（RAAS）。尽管通常是良性的，但RAAS激活在某些女性中可能对肾脏和血流动力学功能产生有害影响。由于经皮贴片（EVRA）联合激素避孕不经过首过肝代谢，我们推测RAAS反应与OCP受试者不同。对35名无心血管疾病、肾脏疾病或糖尿病证据的非吸烟绝经前女性（15名对照受试者、10名OCP受试者和10名避孕贴片受试者）进行了研究。评估了基线血管紧张素原、肾素、血管紧张素II、醛固酮和血浆肾素活性，以及使用递增式下体负压（LBNP；-15、-25和-40 mmHg）对模拟直立位应激的激素和血流动力学反应。与血压正常的对照和避孕贴片受试者相比，OCP受试者的基线血管紧张素原、血管紧张素II和血浆肾素活性水平显著更高（P<0.05），而醛固酮仅在OCP与对照受试者相比时显著更高（P<0.05）。与血压正常的对照和OCP受试者相比，避孕贴片受试者的基线血浆肾素水平显著更低（P<0.05）。对LBNP的反应中，避孕贴片受试者的肾素、血管紧张素II和醛固酮的增加减弱，同时平均动脉压过度下降（与对照和OCP受试者相比，P<0.05）。健康绝经前女性使用避孕贴片与对LBNP反应时维持血压的能力受损有关，可能是由于内源性RAAS不敏感。对肾病女性进行进一步评估可能有益。
